MCH is a hypothalamus-derived hormone known to have an appetite increasing action. Furthermore, it has been reported that MCH knockout mouse behaves normally but shows a significantly decreased food intake amount and a lighter body weight as compared to normal mouse (Nature, vol. 396, page 670, 1998). Furthermore, MCH receptor-1-deficient mice have been reported to show a lean phenotype (Proc. Natl. Acad. Sci. USA, vol. 99, page 3240, 2002). Therefrom MCH receptor (particularly MCH receptor 1) antagonists are expected to be superior appetite suppressants or anti-obesity agents.
As compounds having a MCH receptor antagonistic action, the following compounds are known.
1) WO2007/029847 (patent document 1) discloses a pyridone derivative represented by the formula:
whereinR1 and R2 are the same or different and each is a hydrogen atom, a lower alkyl group optionally having substituent(s) or a lower cycloalkyl group optionally having substituent(s), or R1 and R2 form, together with the nitrogen atom bonded thereto, an aliphatic nitrogen-containing heterocycle optionally having substituent(s),X1, X2 and X3 are the same or different and each is a methine group optionally having substituent(s) or a nitrogen atom, provided that X1, X2 and X3 are not simultaneously nitrogen atoms,Y1 is a single bond, —O—, —NR—, —S—, —SO— or —SO2—,Y2 is a lower alkylene group optionally having substituent(s), a lower alkenylene group optionally having substituent(s) or a lower cycloalkylene group optionally having substituent(s),Y3 is a single bond, —O—, —NR—, —S—, —SO— or —SO2—,each R is independently a hydrogen atom or a lower alkyl group optionally having substituent(s),W1, W2, W3 and W4 are the same or different and each is a single bond, a methylene group optionally having substituent(s) or —O—, provided that continuous two or more of W1, W2, W3 and W4 are not simultaneously —O—,L is a single bond, a methylene group optionally having substituent(s) or an ethylene group optionally having substituent(s), and L optionally forms, together with Z2, R1 and the nitrogen atom bonded to R2, an aliphatic nitrogen-containing heterocycle optionally having substituent(s),Z1 and Z2 are the same or different, and each is a single bond, a C1-4 alkylene group optionally having substituent(s) or —O—,Ar1 is an aromatic carbocyclic group optionally having substituent(s) or an aromatic heterocyclic group optionally having substituent(s), andAr2 is a divalent and bicyclic aromatic carbocyclic group optionally having substituent(s) or a divalent and bicyclic aromatic heterocyclic group optionally having substituent(s), or a pharmaceutically acceptable salt thereof.2) WO2008/086409 (patent document 2) discloses a compound represented by the following formula:
whereinn is 1 or 2,R is NR1R2, wherein R1 and R2 are each independently selected from H and optionally substituted alkyl, or R1 and R2 form, together with the adjacent N atom, a 4- to 7-membered optionally substituted heterocycle optionally containing 1 or 2 hetero atoms in addition to the N atom shown,R3 and R4 are each independently selected from H and alkyl, orR, R3 and R4 may combine to form an optionally substituted imidazolin-2-yl,B is aryl or heteroaryl, andR5, R6 and R7 are each independently selected from H, —OH, —O— alkyl, alkyl, halo, —CF3 and —CN,provided the aforementioned compound is not any of the following
3) Bioorg. Med. Chem. Lett., 20(23), 7015-7019 (2010) (non-patent document 1) discloses a compound represented by the following formula:
wherein R is phenyl, 4-fluorophenyl, 4-chlorophenyl, 2-chlorophenyl, 3-chlorophenyl, 2,4-dichlorophenyl, 4-chloro-2-fluorophenyl, 4-chloro-2-methoxyphenyl, pyridin-2-yl or pyrimidin-2-yl.4) WO2011/130086 (patent document 3) and WO2011/127643 (patent document 4) disclose a compound represented by the formula:
whereinR1 and R2 are each independently selected from the group consisting of halogen, hydrogen, —OH, C1-C6 alkyl, —OC1-C6 alkyl, —O-halogen-substituted C1-C6 alkyl and halogen-substituted C1-C6 alkyl;W is —N— or —CH—;Q is —O—, —NH— or —C—, or forms heteroaryl together with R4, aromatic ring B and R3;R3 is halogen, hydrogen, —OC1-C6 alkyl, C1-C6 alkyl, —O-halogen substituted C1-C6 alkyl, halogen-substituted C1-C6 alkyl, cyano, SO2C1-C6 alkyl or forms a heteroaryl ring together with aromatic ring B, Q and R4;R4 is hydrogen, oxo, C1-C6 alkyl, halogen-substituted C1-C6 alkyl or forms heteroaryl together with aromatic ring B, R3 and Q, or forms C3-C6 cycloalkyl together with R5;R5, R6 and R7 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, halogen-substituted C1-C6 alkyl, C3-C6 cycloalkyl, halogen-substituted C3-C6 cycloalkyl, C1-C6 alkyl C3-C6 cycloalkyl, —OH, C1-C6 alkyl-OH and —OC1-C6 alkyl, or R5 forms oxo group or C3-C6 cycloalkyl together with R6, or R5 forms C3-C6 cycloalkyl together with R4, and at least one of R5, R6 and R7 is not hydrogen, andn is 1-3,or a pharmaceutically acceptable salt thereof.5) WO2010/104830 (patent document 5) discloses a compound represented by the formula
or a salt thereof.6) WO01/82925 (patent document 6) discloses a compound represented by the formula:
whereinAr1 is a cyclic group optionally having substituent(s);X and Y are the same or different and each is a spacer having a main chain of 1 to 6 atoms;Ar is a fused polycyclic aromatic ring optionally having substituent(s);R1 and R2 are the same or different and each is a hydrogen atom or a hydrocarbon group optionally having substituent(s), R1 and R2 optionally form, together with the adjacent nitrogen atom, a nitrogen-containing heterocycle optionally having substituent(s), R2 optionally form, together with the adjacent nitrogen atom and Y, a nitrogen-containing heterocycle optionally having substituent(s), or R2 optionally form, together with the adjacent nitrogen atom, Y and Ar, a nitrogen-containing fused ring optionally having substituent(s), or a salt thereof.7) WO2006/118320 (patent document 7) discloses a compound represented by the formula:
whereinAr is an optionally substituted ring;A is a spacer having a main chain of 1 to 4 atoms;B is a bond, a C1-10 alkylene group or an oxygen atom;R3 and R5 are each independently a hydrogen atom or a substituent;R4 is an optionally substituted cyclic group or an optionally substituted C1-10 alkyl group;R1 and R2 are each independently a hydrogen atom or a substituent, or R1 is bonded to R2 or B to form an optionally substituted nitrogen-containing heterocycle, or R1 is bonded to Ar to form an optionally substituted nitrogen-containing fused heterocycle,or a salt thereof.8) As a γ secretase modulator, WO2009/076352 (patent document 8) discloses, for example, a compound represented by the following formula:
9) Also, as a furan fused pyridinone, Synthesis, 2010, 10, 1741-1744 (non-patent document 2) discloses a compound represented by the following formula:
10) Moreover, the following compound A (CAS Registry Number 885901-19-9) and compound B (CAS Registry Number 885901-16-6) are known.
